Analysis of autoimmune mechanisms of myelodysplastic syndromes

再生障碍性贫血（AA）患者常发生骨髓增生异常综合征（MDS）等克隆性疾病。尽管对潜在的机制知之甚少，但参与AA发病机制的细胞毒性T细胞的一些逃逸与MDS的进展有关。在这项研究中，通过对AA体细胞突变的全面分析，我们发现多达60%的AA患者存在多种基因的频繁体细胞突变。一些突变影响MDS中已知的突变靶点，如DNMT3A、ASXL1和BCOR。这些突变靶点可能代表了AA中CTL的共同靶点，其突变后不仅参与了逃避CTL的过程，而且参与了MDS的克隆选择。在未来的研究中，应该保证测试这些突变靶点是否编码由AA中的CTL识别的共同表位。

It was well known that many patients with aplastic anemia (AA) develop clonal disorders including myelodysplastic syndromes (MDS). Although the underlying mechanism is poorly understood, some escape from cytotoxic T-cells involved in AA pathogenesis is implicated in the progression to MDS. In this study, through a comprehensive analysis of somatic mutations in AA, we identified frequent somatic mutations of a wide variety of genes in as many as 60% of patients with AA. Some mutations affected known mutational targets in MDS, such as DNMT3A, ASXL1, and BCOR. Our results may indicated that these mutational targets could represent common targets of CTLs in AA, which when mutated, involved not only in escaping from CTL but also in clonal selection in MDS. It should be warranted in future studies to test whether these mutational targets encode common epitopes that are recognized by CTLs in AA.